DESCRIPTION Peroxynitrite is formed physiologically from the reaction of superoxide radical anion (O2-) and nitric oxide neutral radical (NO). Both radicals are produced by activated macrophages and neutrophils. Peroxynitrite is not stable and isomerizes to nitrate. Both peroxynitrite and peroxynitrous acid (pKa = 6.8) are oxidants. These oxidants are very reactive with functional groups present in biomolecules and may cause significant and continuous damage to biomolecules in vivo since superoxide is continuously produced both intentionally and as an unwanted by-product of normal oxidative metabolism and nitric oxide, recently discovered to be a new type of neurotransmitter, is continuously present in vivo. Work in the lab of the U.S. P.I. is focused on studying the solution phase reactions of peroxynitrite and peroxynitrous acid under physiological types of conditions. Significant progress has already been made in this research, such as the discovery that peroxynitrous acid can oxidize methionine by at least two different mechanisms, a direct bimolecular reaction and one-electron multi-step electron transfer radical process. These significant studies probably only scratch the surface of the mechanistic complexity involved in oxidation reactions performed by peroxynitrous acid. One important observation is that in the course of the isomerization of peroxynitrous acid to nitric acid an unstable intermediate is formed which is a very strong oxidant. Although work in the Pryor lab will be able to characterize the pattern of reactivity of this intermediate, it is too unstable to be observed directly for structure determination. The proposed gas phase and theoretical work in the lab of Klasinc is designed to examine the isomerization of peroxynitrous acid to nitric acid, to gain some insight into possible structures for the unstable intermediate and to assess the role of solvation, especially the possible covalent intervention of water molecules in the mechanism. The specific aims of the FIRCA are: (1) synthesize peroxynitrite in the gas phase and study its gas phase properties, (2) determine the structure and properties of ONOOH, ONOO, and ONOO with sophisticated quantum chemical calculations within and beyond the Hartree-Fock limit, (3) model quantum chemically the formation and decomposition of ONOOH, ONOO, and ONOO from various reactions in the gas phase, and (4) model quantum chemically the isomerization of ONOOH.